There is strong evidence that the destruction of syngeneic tumors may be mediated by at least three distinct effector mechanisms which involve T cells, null cells and macrophages as the effectors. There is also evidence that each of these effector mechanisms can be and are suppressed in tumor-bearing hosts by suppressive factors released by the tumors or by suppressor cells induced by direct contact with tumors. The objective of this project is to examine the interactions of phenotypically distinct subpopulations of cells which are involved in the generation and suppression of three different immune mechanisms effecting the destruction of syngeneic tumors. The basic approach is to examine the mechanism of generation of effectors and suppressors of tumor destruction, with key focus being on the identification of distinct differentiation and activation lymphokines and phenotypic identification and isolation of the cells producing the factors. The interaction of the helper and suppressor systems will be examined in the context of whether the suppressor factors interfere with production of, or responsiveness to, the differentiation or activation factors of the cytotoxic effectors of tumor destruction and vice versa. The goal is to reveal contrasuppressive interactions which would reduce the suppressive influence of syngeneic tumors on the immune system.